Trial record 11 of 229 for:    Thrombocytopenia: Clinical Trials

Secondary Prophylaxis in Non-Hodgkin Lymphoma (NHL) and Chemotherapy-induced Thrombocytopenia (ProRom)

This study is currently recruiting participants.
Verified January 2012 by IRCCS San Raffaele
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Andres J. M. Ferreri, IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT01516619
First received: January 8, 2012
Last updated: January 24, 2012
Last verified: January 2012
  Purpose

This is a monocentric, prospective phase II trial addressing safety and capability to prevent grade-4 Chemotherapy-induced Thrombocytopenia (CIT) of romiplostim in patients with NHL.


Condition Intervention Phase
Non-Hodgkin Lymphoma
Drug: Romiplostim
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Pilot Phase II Trial on Safety and Activity of Secondary Prophylaxis With Romiplostim in Patients With Non-Hodgkin Lymphoma and Chemotherapy-induced Thrombocytopenia

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • safety [ Time Frame: participants will be followed for the duration of experimental treatment, an expected average of 6 months ] [ Designated as safety issue: Yes ]
    evaluation of safety, defined by the incidence of grade >/= 4 adverse events (NCI CTCAE v. 4.02 Dec 2009)


Secondary Outcome Measures:
  • activity [ Time Frame: From date of registration until the completion of chemotherapy treatment, an expected average of 6 months ] [ Designated as safety issue: Yes ]
    activity defined by the incidence of grade 4 CIT (</= 25 x 10E9/L) per chemotherapy course during experimental treatment


Estimated Enrollment: 20
Study Start Date: November 2011
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: romiplostim Drug: Romiplostim

Romiplostim will be administered subcutaneously at a dose of 250 μg on the 1st, 3rd and 5th days after the last day of chemotherapy delivery and, then, every two days until the achievement of 75.000 plt/μL.

In the case of unsuccessful use of romiplostim after the second chemotherapy course, dose escalation to 500 μg/day, with the same above-mentioned schedule, will be indicated after the third course and for all the further courses, with a maximum of 8.

Other Names:
  • chemotherapy-induced thrombocytopenia
  • Nplate

Detailed Description:

High-dose chemotherapy followed by autologous stem cell transplant is considered standard of care for patients with relapsed and/or refractory aggressive lymphomas. High-dose chemotherapy, with or without ASCT, may also be used as upfront chemotherapy according to lymphoma histotype (e.g. primary central nervous system lymphomas, mantle cell lymphomas), advanced stage disease, extranodal involvement, and high IPI. Chemotherapy-induced myelosuppression results in various degrees of neutropenia, anemia, and thrombocytopenia and related complications can lead to hospitalization, impaired quality of life, death, and increased healthcare costs.

While myeloid growth factors have reduced neutropenia and the incidence of neutropenic fever, and erythropoietic agents have reduced anemia and transfusions, chemotherapy-induced thrombocytopenia (CIT) still remains an unmet treatment need.

Thrombocytopenia is significantly associated with increased bleeding risk, platelet transfusions need, chemotherapy dose reductions and treatment delays, which usually compromise therapeutic efficacy. Platelet transfusions are also limited by cost, supply, and associated risks, such as transfusion reactions, transmission of infection, alloimmunization and platelet refractoriness. Alternative strategies are evaluating pharmacologic options to stimulate platelet production and to overcome CIT.

The predominant reason for a low platelet count in cancer patients receiving chemotherapy is a deficiency in platelet production. Megakaryopoiesis, the process of development of mega-karyocytes and production of platelets, involves a highly complex cascade of events, from differentiation of immature progenitors to maturation of megakaryocytes and release of platelets into the bone marrow sinusoids. Cytokines present within specialized bone marrow niches contribute to survival, proliferation, and differentiation of megakaryocytes. In addition to TPO, an essential growth factor for platelet production, there are several other growth factors and cytokines, such as IL-1, IL-3, IL-6, IL-11, and SCF, that contribute towards megakaryopoiesis at different stages of development and maturation. In the last decade, a number of these cytokines have been evaluated for the prevention and treatment of thrombocytopenia. Unfortunately, none has yet provided a commercially available agent with a high therapeutic index.

Despite very promising thrombopoietic activity, the clinical development of first-generation recombinant TPOs was halted due to immunogenicity concerns. This led to the development of TPO agonists with no homology to TPO that can bind the TPO receptors and activate signal-ling, leading to increase in platelet production.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with NHL of any histotype, both at diagnosis or at relapse, who experienced grade 4 CIT after the first course of chemotherapy containing high doses of methotrexate, cytarabine, cisplatin, cyclophosphamide and/or ifosfamide, and/or conventional doses of anthracyclines or purine analogs, with or without rituximab. The same type of chemotherapy where the grade 4 CIT occurred will be continued at the same planned doses for a maximum of 8 courses.
  • ECOG performance status score </= 3.
  • Adequate bone marrow function (ANC >1.000; Hb >9,5 g/dL; PLT > 75.000).

Exclusion Criteria:

  • Patients eligible for high-dose chemotherapy, where stem cell support is planned.
  • Thrombotic events in the previous 5 years before enrolment.
  • Other malignancies diagnosed in the previous 5 years before enrolment.
  • Severe concomitant illnesses/medical conditions (e.g. impaired respiratory and/or cardiac function, uncontrolled diabetes mellitus).
  • Active infectious disease.
  • Impaired liver function (bilirubin >2 x upper normal limit; ALT/AST/GGT > 3 x upper normal limit) at one month from salvage chemotherapy conclusion.
  • Impaired renal function (creatinine clearance <50 ml/min) at one month from salvage chemotherapy conclusion.
  • Non-cooperative behavior or non-compliance.
  • Psychiatric diseases or conditions that might impair the ability to give informed consent.
  • Pregnant or lactating females.
  • Previous therapy with any TPO-mimetic or similar substances.
  • Previous therapy supported by transplant of autologous or allogeneic stem cells
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01516619

Contacts
Contact: Andrés JM Ferreri, MD +39022643 ext 7649 ferreri.andres@hsr.it
Contact: Silvia Govi, MD +39022643 ext 7612 govi.silvia@hsr.it

Locations
Italy
Dip. Oncoematologia - Fondazione Centro San Raffaele del Monte Tabor Recruiting
Milano, Italy
Contact: Andrés JM Ferreri, MD    +39022643 ext 7649    ferreri.andres@hsr.it   
Contact: Silvia Govi, MD    +39022643 ext 7612    govi.silvia@hsr.it   
Principal Investigator: Andrés JM Ferreri, MD         
Sponsors and Collaborators
Andres J. M. Ferreri
Amgen
Investigators
Study Chair: Andrés JM Ferreri, MD San Raffaele Scientific Institute, Milano, Italy
  More Information

No publications provided

Responsible Party: Andres J. M. Ferreri, MD, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT01516619     History of Changes
Other Study ID Numbers: ProRom
Study First Received: January 8, 2012
Last Updated: January 24, 2012
Health Authority: Italy: Ethics Committee
Italy: The Italian Medicines Agency

Keywords provided by IRCCS San Raffaele:
NHL
chemotherapy-induced grade-4 thrombocytopenia

Additional relevant MeSH terms:
Thrombocytopenia
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blood Platelet Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on April 22, 2014